Modified release pharmaceutical dosage forms have long been used to optimize drug delivery and enhance patient compliance, especially by reducing the number of doses of medicine the patient must take in a day. Well known mechanisms by which a dosage form (or drug delivery system) can deliver drug at a modified rate (e.g. sustained or delayed release) include diffusion, erosion, and osmosis. An important objective of modified release dosage forms is to provide a desired blood concentration versus time profile for the drug. Fundamentally, the pharmacokinetic profile for a drug is governed by the rate of absorption of the drug into the blood, and the rate of elimination of the drug from the blood. To be absorbed into the blood (circulatory system), the drug must first be dissolved in the gastrointestinal fluids. For those relatively rapidly absorbed drugs whose dissolution in gastrointestinal fluids is the rate limiting step in drug absorption, controlling the rate of dissolution (i.e. drug release from the dosage form) allows the formulator to control the rate of drug absorption into the circulatory system of a patient. The type of PK profile, and correspondingly, the type of dissolution or release profile desired, depends on, among other factors, the particular pharmaceutically active agent and physiological condition being treated.
U.S. Pat. No. 6,228,398 discloses solid dosage forms which contain a multiparticulate system of modified release and immediate release pharmaceutically active agents such that the pharmaceutically active agent is supplied in a pulsatile manner. However, multiparticulate systems disadvantageously have the added cost and processing associated with adding modified release layers to particulates which contain the pharmaceutically active agents.
U.S. Pat. No. 7,157,100 discloses solid dosage forms which contain multiple layers wherein one or more layers contains pharmaceutically active agent to be delivered in an immediate release manner and one or more layers contains pharmaceutically active agent to be displayed in a modified release manner. The dosage form delivers the pharmaceutically active agent such that the composition can be supplied in a once per day dosing regimen. However, multiple layers of a dosage form must be prepared in multiple stations and with multiple blends, adding complexity to the preparation of the dosage form.
Thus, there is a need to develop a process for making a tablet wherein both an immediate release region and the modified release region can be made from the same powder blend.